A humanized anti-DLL4 antibody promotes dysfunctional angiogenesis and inhibits breast tumor growth

@article{Jia2016AHA,
  title={A humanized anti-DLL4 antibody promotes dysfunctional angiogenesis and inhibits breast tumor growth},
  author={Xuelian Jia and Wenyi Wang and Zhuobin Xu and Shijing Wang and Tong Wang and Min Wang and Min Wu},
  journal={Scientific Reports},
  year={2016},
  volume={6}
}
Blockage of Delta-like 4 (DLL4)-directed Notch signaling induces excessive tip cell formation and endothelial proliferation resulting in dysfunctional angiogenesis in tumors. MMGZ01, as a murine anti-human DLL4 monoclonal antibody, specifically binds to human DLL4 and blocks Notch pathway. Here, the structure of MMGZ01 variable fragment (Fv) was established and framework region (FR) residues which supported complementarily determining region (CDR) loop conformation were identified. Important… 
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24 Citations
Background Citations
6
Methods Citations
2
Results Citations
1

24 Citations

Generation and characterization of an anti-delta like ligand-4 Nanobody to induce non-productive angiogenesis.
The bispecific antibody HB-32, blockade of both VEGF and DLL4 shows potent anti-angiogenic activity in vitro and anti-tumor activity in breast cancer xenograft models.
DR-5 and DLL-4 mAb Functionalized SLNs of Gamma-Secretase Inhibitors- An Approach for TNBC Treatment
TLDR
Solid lipid nanoparticles based drug delivery systems containing GSIs and surface modified with DR-5 and DLL4 monoclonal antibodies to effectivity target and treat TNBC are discussed.
Two engineered site-specific antibody-drug conjugates, HLmD4 and HLvM4, have potent therapeutic activity in two DLL4-positive tumour xenograft models.
TLDR
The engineered anti-DLL4 ADCs, particularly HLmD 4, showed more potent antitumour activity than Docetaxel and superior safety compared with JmD4 in two xenograft tumour models, indicating that engineered ADCs have promising potential as effective preclinical therapies for cancers.
Notch signaling triggered via the ligand DLL4 impedes M2 macrophage differentiation and promotes their apoptosis
TLDR
Interplay between the DLL4/Notch and IL-4/IL-4R signaling pathways impairs M2 differentiation and may drive a Notch-dependent selection process not only by promoting M1 macrophage differentiation but also by preventing M2 macrophages differentiation through inhibition of M2-specific gene expression and apoptotic cell death.
Notch signaling regulates vessel structure and function via Hspg2
Therapeutic Targeting of Notch Signaling: From Cancer to Inflammatory Disorders
TLDR
Te lessons learned are emphasized to provide guidance about emerging strategies of Notch-based therapeutics that could be deployed safely and efficiently in patients with immune and inflammatory disorders.
The complexity of tumour angiogenesis based on recently described molecules
TLDR
Novel discoveries related to the less known angiogenic molecules such as galectins, pentraxin-3, Ral-interacting protein of 76 kDa (RLIP76), long non-coding RNAs, B7-H3, and delta-like ligand-4 (DLL-4) are summarized and their role in the process of tumour angiogenesis is discussed.
Context Matters: NOTCH Signatures and Pathway in Cancer Progression and Metastasis
TLDR
Altered Notch signaling hereby plays a key role for tumor cell survival and coping with a broad spectrum of vital issues, contributing to failed therapies, poor patient outcome, and loss of lives.
Frequent Activation of Notch Signaling Pathway in Colorectal Cancers and Its Implication in Patient Survival Outcome
TLDR
Taken together, Notch signaling components are aberrantly overexpressed in colorectal tumors, and development of therapeutics targeting the Notch pathway may prove to be beneficial in the management of coloreCTal cancers.
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References

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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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